Evidence links KRAS mutations to poor survival in colorectal cancer

KRAS gene mutations are strong predictors of reduced overall survival and progression-free survival and increased rates of treatment failure in patients with advanced colorectal cancer undergoing anti-EGFR therapy, according to a recent analysis.

As Thomas A. Trikalinos, MD, of the Institute for Clinical Research and Health Policy Studies at Tufts Medical Center, and fellow researchers noted in their report, KRAS mutations have been extensively investigated as predictive biomarkers for treatment of advanced colorectal cancer with anti-epidermal growth factor (EGFR) antibodies cetuximab and panitumumab (Ann Intern Med. 2011;154:37-49, available at www.annals.org/content/154/1/37.full.pdf+html?sid=987d8a36-9b7e-49f2-a812-049e38d7c7b8). The EGFR gene, which is considered a good candidate for targeted cancer therapy, is frequently amplified in colorectal cancer.

Dr. Trikalinos' team undertook a review of data from various trials to determine whether KRAS mutation status modifies effects of anti-EGFR-based treatments for advanced colorectal cancer and whether KRAS status predicts clinical outcomes in such patients. In four reanalyses of randomized trials of anti-EGFR-based therapy vs. best supportive care or cytotoxic chemotherapy, the investigators found no significant benefit for overall or progression-free survival from anti-EGFR-based treatment among KRAS-positive patients. They found the benefits of this therapy to be largely limited to KRAS wild-type patients, particularly in terms of progression-free survival and response to treatment.